Stereological analysis of hippocampus in rat treated with chemotherapeutic agent oxaliplatin.

BACKGROUND: Oxaliplatin (OX) has been widely used for treatment of colorectal and other cancers. Adverse effect of OX and other anticancer agents on cognition have been reported, but studies on the effects of chemotherapy on brain structure are scarce. This study describes the morphometrical features of the hippocampus structures in rat following OX treatment using design-based stereological methods. MATERIALS AND METHODS: Ten male Wistar rats were randomised into two groups. The rats from OX group received 2.4 mg/kg OX in vehicle for 5 consecutive days every week for 2 weeks intraperitoneally. Controls received vehicle only. Cavalieri's method and the optical fractionator method were used for volume and neuron estimation, respectively. RESULTS: Cavalieri's method was used to estimate volume and showed that the volume of the hippocampus was significantly decreased in OX group (31.84 ± ± 1.24 mm3) compared with the vehicle control group (36.95 ± 3.48 mm3). The optical fractionator method was used to estimate neuron number and showed that the number of neurons in dentate gyrus, cornu ammonis 1 and 3 in OX group (8.147 ± 2.84 × 105, 4.257 ± 0.59 × 105 and 2.133 ± 0.22 × 105, respectively) did not differ from those of vehicle control group (7.36 ± 1.42 × 105, 3.521 ± ± 0.54 × 105 and 1.989 ± 0.46 × 105, respectively). CONCLUSIONS: These findings suggested that OX treatment induces loss of hippocampal volume without neuronal loss which might help to clarify the mechanism by which OX affects cognition and to improve preventive treatment strategies.

Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.

Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species.

Number estimates of neuronal phenotypes in layer II of the medial entorhinal cortex of rat and mouse.

Modelling entorhinal function or evaluating the consequences of neuronal losses which accompany neurodegenerative disorders requires detailed information on the quantitative cellular composition of the normal entorhinal cortex. Using design-based stereological methods, we estimated the numbers, proportions, densities and sectional areas of layer II cells in the medial entorhinal area (MEA), and its constituent caudal entorhinal (CE) and medial entorhinal (ME) fields, in the rat and mouse. We estimated layer II of the MEA to contain approximately 58,000 neurons in the rat and approximately 24,000 neurons in the mouse. Field CE accounted for more than three-quarters of the total neuron population in both species. In the rat, layer II of the MEA is comprised of 38% ovoid stellate cells, 29% polygonal stellate cells and 17% pyramidal cells. The remainder is comprised of much smaller populations of horizontal bipolar, tripolar, oblique pyramidal and small round cells. In the mouse, MEA layer II is comprised of 52% ovoid stellate cells, 22% polygonal stellate cells and 14% pyramidal cells. Significant species differences in the proportions of ovoid and polygonal stellate cells suggest differences in physiological and functional properties. The majority of MEA layer II cells contribute to the entorhinal-hippocampal pathways. The degree of divergence from MEA layer II cells to the dentate granule cells was similar in the rat and mouse. In both rat and mouse, the only dorsoventral difference we observed is a gradient in polygonal stellate cell sectional area, which may relate to the dorsoventral increase in the size and spacing of individual neuronal firing fields. In summary, we found species-specific cellular compositions of MEA layer II, while, within a species, quantitative parameters other than cell size are stable along the dorsoventral and mediolateral axis of the MEA.

No evidence for loss of hippocampal neurons in non-Alzheimer dementia patients.

OBJECTIVE: To use stereological methods for estimating the total number of neurons in hippocampi of non-Alzheimer demented patients. MATERIAL AND METHODS: Hippocampi from six women with severely impaired memory but without Alzheimer pathology were compared with six mentally intact age-matched female controls. The total number of neurons was estimated in the granule cell layer of the dentate gyrus, the hilus of the dentate gyrus, the pyramidal cell layer of CA3 and CA2, the pyramidal cell layer of CA1 and the cellular layer of subiculum using the optical fractionator. RESULTS: The total neuron number was the same in the dementia cases, 22.4 x 106, compared with 22.7 x 106 in the controls (P = 0.85). No region-specific group differences or side difference were found. Two cases without clinical signs of dementia but with abundant plaques and tangles in hippocampus and neocortex had total neuron numbers within normal limits. CONCLUSION: Our results indicate that severely impaired memory can occur in the presence of intact numbers of hippocampal neurons in non-Alzheimer dementia and that nerve cell loss in the hippocampus might be characteristic for Alzheimer's disease, and perhaps other forms of primary cortical dementia.

[Analysis of the activity of neurologic intensive care units]. / Neurológiai intenzív részlegek müködésének elemzése.

The authors analysed six-year activity of the intensive Care Unit of Department of Neurology, Medical University of Pécs (POTEI), and two-year activity of the Intensive Care Unit of Department of Neurology, Semmelweis University of Medicine, Budapest (SOTEI). Mortality at POTEI and SOTEI was 33.9% and 32.2%, respectively. Mean duration of stay of survivors at POTEI was 10 +/- 12.8 days, and 7 +/- 6.8 days at SOTEI; mean duration of care of the deceased patients at POTEI was 6.3 +/- 10.5 days, and 10 +/- 13.7 days at SOTEI. At POTEI 60.7%, at SOTEI 63% of the patients was admitted because of cerebrovascular insult. Mortality of patients with brain haemorrhage at POTEI and SOTEI was 53.4% and 57.7% respectively. Mortality of the ischaemic group was 40.6% (POTEI) and 35.3% (SOTEI). In the group of intracranial tumours 44.4% mortality was recorded at POTEI and 47.6% at SOTEI. At POTEI 240 patients (15.9%), while at SOTEI 94 patients (21%) were admitted to treat epileptic seizures. Among the 510 patients, who died within one month 284 patients (55.6%) were unconscious at admission. From those with coma due to severe structural lesion of the brain (brain ischaemia, bleeding, meningitis) only 15 patients survived. Among the 184 patients, who were comatose and survived, the most frequent diagnosis was suicidal attempt with hypnotics (n = 67), metabolic encephalopathy (n = 19) and epilepsy (n = 12). At SOTEI among the 144 deceased patients 102 (70.8%) were unconscious at admission. Coma at admission proved to be a strong predictor of mortality. Mortality of the ventilated patients was 83% at POTEI and of those having subclavian catheter (n = 592) was 47.1%. In the acute phase of brain ischaemia at POTEI 39%, at SOTEI 10.7% of the patients received heparin. At SOTEI the cost of medication of patients who died after two weeks of care was 65.2% higher than that of the survived patients.

Mortality after operation for hiatus hernia.

When we started this investigation we were convinced that we would not be able to collect enough fatal cases to enable us to analyse the various causes of death following operation for hiatus hernia. To our surprise, inquiries made at 53 paediatric surgical centres produced a total of 67 fatalities. Most of these deaths could have been prevented if the following rules would have been followed: 1. The diagnosis must be made early and therapy must be commenced as soon as possible before there is a deterioration of the patient's general state of health increasing the risk of operation. 2. It is important to be familiar with the various operative techniques and the possible complications which they can produce. 3. Follow-up examinations are essential as certain complications will be detected by the patient himself only too late! Mortality and morbidity of hiatus hernia should be very small if the correct treatment has been carried out. Nissen's fundoplication, Rehbein's hiatal plasty and gastropexy, Lortat-Jacob/Grob's oesophagogastropexy and their modifications, all carry a low mortality and are followed by good results stopping the gastro-oesophageal reflux.